Biologic consequences of Stat1-independent IFN signaling

Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6680-5. doi: 10.1073/pnas.111163898.


Although Stat1 is required for many IFN-dependent responses, recent work has shown that IFNgamma functions independently of Stat1 to affect the growth of tumor cells or immortalized fibroblasts. We now demonstrate that both IFNgamma and IFNalpha/beta regulate proliferative responses in cells of the mononuclear phagocyte lineage derived from Stat1-null mice. Using both representational difference analysis and gene arrays, we show that IFNgamma exerts its Stat1-independent actions on mononuclear phagocytes by regulating the expression of many genes. This result was confirmed by monitoring changes in expression and function of the corresponding gene products. Regulation of the expression of these genes requires the IFNgamma receptor and Jak1. The physiologic relevance of IFN-dependent, Stat1-independent signaling was demonstrated by monitoring antiviral responses in Stat1-null mice. Thus, the IFN receptors engage alternative Stat1-independent signaling pathways that have important physiological consequences.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Division / drug effects
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation / drug effects
  • Humans
  • Interferons / pharmacology*
  • Janus Kinase 1
  • Macrophages / metabolism
  • Mice
  • Protein-Tyrosine Kinases / physiology
  • Receptors, Interferon / physiology
  • STAT1 Transcription Factor
  • Trans-Activators / physiology*


  • DNA-Binding Proteins
  • Receptors, Interferon
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Stat1 protein, mouse
  • Trans-Activators
  • interferon gamma receptor
  • Interferons
  • Protein-Tyrosine Kinases
  • JAK1 protein, human
  • Jak1 protein, mouse
  • Janus Kinase 1